Although morphine is an extremely important pharmacologic agent used in the treatment of cardiac patients, an understanding of the mechanisms by which it produces changes in the circulation are still controversial. Part of the problem is that the circulatory response to narcotics may be qualitatively as well as quantitatively different in different species. Thus, most of the studies described in this research proposal involve the evaluation of the effects of morphine and related narcotics on specific circulations in human subjects (splanchnic, coronary, and limb). This research project will seek to answer two major questions: (1) Does morphine induce a peripheral pooling of blood in the splanchnic circulation? (2) Does morphine exert its peripheral vasodilation effect by altering the vasoconstrictor response to chemoreceptor stimulation? The first question can only be approached by first developing a technique for the evaluation of splanchnic blood volume. Two techniques are proposed. The first involves the use of two indicators, indocyanine green dye to measure splanchnic blood flow, and Evans blue dye to determine splanchnic mean transit time. The second technique to evaluate changes in splanchnic blood volume involves a series of Evans blue dye curves across the splanchnic, renal, and lower limb circulations to selectively isolate changes in splanchnic blood volume that occur with interventions. Following development of these changes in splanchnic blood volume induced by 45 degrees head-up tilt will be evaluated before and after the administration of morphine and related narcotics. Since isolated chemoreceptor stimulation cannot be achieved in humans, three animal models will be evaluated to determine the effects of morphine on total systemic, skeletal muscle, and cutaneous vascular resistance that are induced by carotid body hypoxia and hypercapnia. The animals studied will be the dog, the Irus monkey, and the domestic swine. Thus, these studies hope to more precisely define the mechanism by which narcotics produce an arteriolar dilation and to determine if they have the ability to produce significant pooling of blood in the splanchnic circulation.